This project employs animal models (rats, rabbits and dogs) to investigate the biological effects of orally or intravenously administered insulin entrapped in liposomes, which are synthetic microscopic aggregates of lipids arranged in a lamellar fashion about a series of aqueous layers containing the hormone. In preliminary studies we have demonstrated incorporation of insulin into liposomes, and biological effectiveness following intravenous administration; the duration of hypoglycemic effect appears to be substantially longer as compared to regular insulin. Preliminary studies also indicate absorption and biological effectiveness of orally administered liposome-entrapped insulin (LEI) in some instances, particularly when the liposomes are negatively charged. In ongoing studies we will examine further the kinetics of action of LEI given orally and intravenously, their efficacy and toxicity and their fate and distribution through studies with tracer-labeled LEI and biopsy of selected tissue for electron microscopy, in normal or chemically induced diabetic animals.